We present a highly active CeO 2 -based catalyst for oxidizing CO in automobile exhaust. This catalyst was systemically designed by co-doping with transition metals (TMs). First, we used density functional theory (DFT) calculations to screen Mn and 13 dopant TMs (periods 4~6 in groups VIII~XI) and their 91 binary combinations for co-doping. As a result, Cu and (Cu, Ag) were found to be the best candidates among the single and binary dopants, respectively. Next, we synthesized CeO 2 nano-particles doped with Cu or (Cu, Ag), then experimentally confirmed that the predicted (Cu, Ag) co-doped CeO 2 showed higher activity than pure CeO 2 and other TM-doped CeO 2 . This was attributed to the easy formation of oxygen vacancies in the lattice of CeO 2 . Our study demonstrates that the use of a rational design of CeO 2 -based catalyst through theoretical calculations and experimental validation can effectively improve the low-temperature catalytic activity of CO oxidation.